ArticlePharmaceutical research2015
PTD-Modified ATTEMPTS for Enhanced Toxin-based Cancer Therapy: An In Vivo Proof-of-Concept Study.
Article in Pharmaceutical research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- Exploring two tumor treatment strategies: effectiveness of ribosome inactivating proteins and mesenchymal stem cells/MSC derived extracellular vesicles in cancer treatment.Frontiers in oncology · 2025Review
- Molecularly engineered tumor acidity-responsive plant toxin gelonin for safe and efficient cancer therapy.Bioactive materials · 2022Article
- Advances on Delivery of Cytotoxic Enzymes as Anticancer Agents.Molecules (Basel, Switzerland) · 2022Review
- Targeted Delivery of Endosomal Escape Peptides to Enhance Immunotoxin Potency and Anti-cancer Efficacy.The AAPS journal · 2022Article
- Cell-penetrating peptides improve pharmacokinetics and pharmacodynamics of anticancer drugs.Tissue barriers · 2022Review
- Enhanced control of bioactivity of tissue plasminogen activator (tPA) through domain-directed enzymatic oxidation of terminal galactose.BioImpacts : BI · 2022Article
- Peptide-Based Drug Delivery Systems.Medicina (Kaunas, Lithuania) · 2021Review
- Delivery of Various Cargos into Cancer Cells and Tissues via Cell-Penetrating Peptides: A Review of the Last Decade.Pharmaceutics · 2021Review
- Toxic proteins application in cancer therapy.Molecular biology reports · 2021Review
- Advances on Tumor-Targeting Delivery of Cytotoxic Proteins.ACS pharmacology & translational science · 2020Review
- Review
- "Catch-and-Release" Anti-Carcinoembryonic Antigen Monoclonal Antibody Leads to Greater Plasma and Tumor Exposure in a Mouse Model of Colorectal Cancer.The Journal of pharmacology and experimental therapeutics · 2018Article
- Improved Protein Toxin Delivery Based on ATTEMPTS Systems.Current drug targets · 2018Review
- Molecular tumor targeting of gelonin by fusion with F3 peptide.Acta pharmacologica Sinica · 2017Article
- Intein-mediated site-specific synthesis of tumor-targeting protein delivery system: Turning PEG dilemma into prodrug-like feature.Biomaterials · 2017Article
- Heparin-Regulated Prodrug-Type Macromolecular Theranostic Systems for Cancer Therapy.Nanotheranostics · 2017Review
- Preparation and Characterization of Gelonin-Melittin Fusion Biotoxin for Synergistically Enhanced Anti-Tumor Activity.Pharmaceutical research · 2016Article
- Augmenting the Efficacy of Immunotoxins and Other Targeted Protein Toxins by Endosomal Escape Enhancers.Toxins · 2016Review
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 6 countries.
Funding
Abstract
purposeTo investigate the feasibility of applying PTD-modified ATTEMPTS (Antibody Targeted Triggered Electrically Modified Prodrug-Type Strategy) for enhanced toxin therapy for the treatment of cancer.
methodsA heparin-functionalized murine anti-CEA monoclonal antibody (mAb), T84.66-heparin (T84.66-Hep), was chemically synthesized and characterized for specific binding to CEA overexpressed cells. The T84.66-Hep was then applied to the PTD-modified ATTEMPTS approach and the crucial features of the drug delivery system (DDS), 'antibody targeting' and 'heparin/protamine-based prodrug', were evaluated in vitro to examine whether it could selective delivery a PTD-modified toxin, recombinant TAT-gelonin chimera (TAT-Gel), to CEA high expression cancer cells (LS174T). Furthermore, the feasibility of the drug delivery system (DDS) was assessed in vivo by biodistribution and efficacy studies using LS174T s.c. xenograft tumor bearing mice.
resultsT84.66-Hep displayed specific binding, but limited internalization (35% after 48 h incubation) to CEA high expression LS174T cells over low expression HCT116 cells. When mixed together with TAT-Gel, the T84.66-Hep formed a strong yet reversible complex. This complex formation provided an effective means of active tumor targeting of TAT-Gel, by 1) directing the TAT-Gel to CEA overexpressed tumor cells and 2) preventing nonspecific cell transduction to non-targeted normal cells. The cell transduction of TAT-Gel could, however, be efficiently reversed by addition of protamine. Feasibility of in vivo tumor targeting and "protamine-induced release" of TAT-Gel from the T84.66-Hep counterpart was confirmed by biodistribution and preliminary efficacy studies.
conclusionsThis study successfully demonstrated in vitro and in vivo the applicability of PTD-modified ATTEMPTS for toxin-based cancer therapy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.